Techniques are rapidly developing for parallel performance of a large number of chemical and biological assays and synthesis operations. One approach uses a nanotiter plate having a high density platen of through-hole wells with hydrophilic interiors and openings surrounded by hydrophobic material. This is described, for example, in U.S. Pat. No. 6,387,331 and U.S. Patent Application 20020094533, the contents of which are incorporated herein by reference. One specific commercial example of a nanotiter plate system is the Living Chip™ made by Biotrove, Inc. of Cambridge, Mass. Nanotiter plate technology relies on the ability to handle very small volumes of fluid samples, typically, 100 nanoliters or less. The various considerations taken into account in handling such small liquid samples are known as microfluidics.
Transferring of large collections of fluids such as libraries of small molecule drug candidates, cells, probe molecules (e.g., oligomers), and/or tissue samples stored in older style 96- or 384-well plates into more efficient high density arrays of microfluidic receptacles such as a nanotiter plate can consume one or more hours, during which time samples may evaporate, degrade or become contaminated. It is therefore advantageous to submerse the array in a bath of immiscible fluid. The fluid is ideally electrically insulating, non-conductive and nonflammable, with a relative permittivity >1. One class of fluids that serves this purpose is perfluorinated hydrocarbons, such a perfluorodecalin, perfluorooctane, perfluoropentane, longer chained perfluorocarbons or mixed populations of perfluorocarbons. Hydrocarbons or silicone fluids would also work but are flammable and tend to extract compounds from the sample.
A microfluidic volume of a liquid sample may be loaded into a target receptacle by various means. One established method for transferring a liquid sample to a surface or to another liquid uses a transfer pin loaded with the sample liquid. For example, pins or arrays of pins are typically used to spot DNA samples onto glass slides for hybridization analysis. Pins have also been used to transfer liquids such as drug candidates between microplates or onto gels (one such gel system is being developed by Discovery Partners, San Diego, Calif.). Many pin types are commercially available, of various geometries and delivery volumes. V&P Scientific of San Diego, Calif. makes slotted, grooved, cross-hatched, and other novel-geometry pins. The Stealth Pin by ArrayIt is capable of delivering hundreds of spots in succession from one sample uptake, with delivery volumes of 0.5 nL to 2.5 nL. Majer Precision Engineering sells pins having tapered tips and slots such as the MicroQuil 2000.
U.S. Pat. No. 6,149,815 describes an approach for dispensing liquid samples electrokinetically. A complex apparatus positions a receiver reservoir and a non-conducting liquid dispenser between a ground plate and a high voltage plate, neither plate being electrically connected to a sample. An accurate volume of liquid sample is transferred from the dispenser to the receiver reservoir by precisely controlling the time that a high voltage is applied to the dispenser, the longer the voltage is applied, the greater the volume of sample transferred, and vice versa. As shown in FIG. 1 of the '815 patent, it is important to provide an insulating gap between the electrically charged dispenser and the electrically grounded receiver reservoir. Moreover, the '815 patent approach requires determining by visual observation the relationship between time, voltage, and volume of liquid transferred. Nonetheless, the '815 patent does suggest that high voltage electric potential may be useful for transferring liquid samples from a loaded transfer pin.